Identification of emerging FLT3 ITD‐positive clones during clinical remission and kinetics of disease relapse in acute myeloid leukaemia with mutated nucleophosmin. (11th March 2013)

• Record Type: Journal Article
• Authors: Ottone, Tiziana; Zaza, Serena; Divona, Mariadomenica; Hasan, Syed Khizer; Lavorgna, Serena; Laterza, Serena; Cicconi, Laura; Panetta, Paola; Giandomenico, Jonny Di; Cittadini, Michela; Ciardi, Claudia; Montefusco, Enrico; Franchi, Annibale; Annino, Luciana; Venditti, Adriano; Amadori, Sergio; Lo‐Coco, Francesco
• Is Part Of: British journal of haematology. Volume 161:Number 4(2013:May)
• Page Start: 533
• Page End: 540
• Publication Date: 2013-03-11
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12288
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12288-abs-0001"> <title>Summary</title> <p> <italic>FLT3</italic> internal tandem duplication (ITD) mutations are frequently detected at diagnosis in cytogenetically normal acute myeloid leukaemia (CN‐AML) and predict unfavourable outcome. <italic>FLT3</italic> ITD is an unstable aberration and may be lost or acquired at relapse. Recent whole genome sequencing studies have suggested that <italic>FLT3</italic> ITD<sup>+</sup>ve AML relapse may evolve from small subclones undetectable at diagnosis by routine polymerase chain reaction (PCR). We developed a patient‐specific real‐time quantitative‐PCR (RQ‐PCR) to implement <italic>FLT3</italic> ITD detection in six AML patients whose blasts carried wild‐type <italic>FLT3</italic> at diagnosis and who relapsed with <italic>FLT3</italic> ITD by routine PCR. Patient‐specific forward primers were designed after cloning and sequencing the <italic>FLT3</italic> ITD in each case. The assay allowed retrospective detection of <italic>FLT3</italic> ITD in diagnostic samples of 4/6 cases and to establish the kinetics of clonal evolution preceding relapse. After conventional chemotherapy, all patients had early relapse despite having been classified as <italic>NPM1</italic><sup>+</sup>ve/<italic>FLT3</italic> ITD<sup>−</sup>ve at presentation, with shorter remissions being observed in four patients re‐classified as <italic>FLT3</italic> ITD<sup>+</sup>ve by the new assay. Notably, <italic>FLT3</italic> ITD clone became detectable by conventional PCR in three patients tested during remission after initial treatment. Our data underscore the need of identifying low <italic>FLT3 </italic>ITD levels, which are probably associated with relapse in otherwise good prognosis CN‐AML.</p> </abstract>